Learning difficulties : a portuguese perspective of a universal issue

In this article we present findings of a study that was conducted with the purpose of deepening the knowledge about the field of learning difficulties in Portugal. Therefore, within these findings we will discuss across several cultural boundaries, themes related with the existence of learning difficulties as a construct, the terminology, the political, social and scientific influences on the field, and the models of identification and of ongoing school support for students. While addressing the above-mentioned themes we will draw attention to the different, yet converging, international understandings of learning difficulties

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Ideações e tentativas de suicídio em adolescentes com práticas sexuais hetero e homoeróticas

Esta pesquisa, que teve como população-alvo adolescentes com idade entre 12 e 20 anos, residentes em três municípios do interior Paulista, buscou conhecer as associações entre orientação sexual e ideações e tentativas de suicídio. Corroborando com as pesquisas internacionais, evidenciou-se que os não heterossexuais têm mais chances de pensarem e tentarem suicídio, comparativamente aos heterossexuais. Todavia, encontrou-se que, dentre o grupo de adolescentes que se assumiram não heterossexuais, os que estão mais vulneráveis são aqueles que se autodefiniram bissexuais e "outros", os quais constituem o grupo de pessoas menos assumidas, dentre os não heterossexuais. Do mesmo modo, constatou-se que os respondentes apresentam diversas opiniões e valores homofóbicos, sexistas e heterocentrados, o que revela ser o espaço escolar, onde se encontram esses jovens não heterossexuais, bastante carregado de posicionamentos discursivos discriminatórios. Conclui-se que a questão do suicídio é uma problemática de saúde pública e que a população de jovens não heterossexuais necessita de abordagens específicas para a prevenção e de atenção relativas a essa conduta.This survey, which had as the target population adolescents aged between 12 and 20 years living in three municipalities in São Paulo, sought to investigate the associations between sexual orientation and ideation and suicide attempts. Confirming international research findings, it is showed that non-heterosexuals are more likely to attempt and think about suicide, compared to heterosexuals. However, we found that among the group of teenagers who assumed to be non-heterosexuals, the most vulnerable are those who define themselves as bisexual and "other", which constitute the group of people less assumed, among non-heterosexuals. Similarly, it was found that the respondents have different homophobic, sexist and heterocentric opinions and values, which turn out to be the school environment, where these young non-heterosexual study, loaded with enough discriminatory discursive positions. We conclude that the issue of suicide is a public health problem and that the population of young non-heterosexual needs specific approaches for prevention and care in respect to this conduct

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p < 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes

RNF4 Regulates the BLM Helicase in Recovery From Replication Fork Collapse

Sumoylation is an important enhancer of responses to DNA replication stress and the SUMO-targeted ubiquitin E3 ligase RNF4 regulates these responses by ubiquitylation of sumoylated DNA damage response factors. The specific targets and functional consequences of RNF4 regulation in response to replication stress, however, have not been fully characterized. Here we demonstrated that RNF4 is required for the restart of DNA replication following prolonged hydroxyurea (HU)-induced replication stress. Contrary to its role in repair of γ-irradiation-induced DNA double-strand breaks (DSBs), our analysis revealed that RNF4 does not significantly impact recognition or repair of replication stress-associated DSBs. Rather, using DNA fiber assays, we found that the firing of new DNA replication origins, which is required for replication restart following prolonged stress, was inhibited in cells depleted of RNF4. We also provided evidence that RNF4 recognizes and ubiquitylates sumoylated Bloom syndrome DNA helicase BLM and thereby promotes its proteosome-mediated turnover at damaged DNA replication forks. Consistent with it being a functionally important RNF4 substrate, co-depletion of BLM rescued defects in the firing of new replication origins observed in cells depleted of RNF4 alone. We concluded that RNF4 acts to remove sumoylated BLM from collapsed DNA replication forks, which is required to facilitate normal resumption of DNA synthesis after prolonged replication fork stalling and collapse. Copyright © 2021 Ellis, Zhu, Yagle, Yang, Huang, Kwako, Seidman and Matunis.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The DNA Translocase FANCM/MHF Promotes Replication Traverse of DNA Interstrand Crosslinks

The replicative machinery encounters many impediments, some of which can be overcome by lesion bypass or replication restart pathways, leaving repair for a later time. However, interstrand crosslinks (ICLs), which preclude DNA unwinding, are considered absolute blocks to replication. Current models suggest that fork collisions, either from one or both sides of an ICL, initiate repair processes required for resumption of replication. To test these proposals, we developed a single molecule technique for visualizing encounters of replication forks with ICLs, as they occur in living cells. Surprisingly, the most frequent patterns were consistent with replication traverse of an ICL, without lesion repair. The traverse frequency was strongly reduced by inactivation of the translocase and DNA binding activities of the FANCM/MHF complex. The results indicate that translocase-based mechanisms enable DNA synthesis to continue past ICLs, and that these lesions are not always absolute blocks to replication

The impact of contrast sensitivity on performance on the Sonksen Picture Guide to Visual Function

0ntbrkt